Is ATAD5 p.Pro87Ser (c.259C>T) pathogenic?

ATAD5 p.Pro87Ser (c.259C>T) is classified Benign in ATAD5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-18). AlphaMissense: likely benign (0.0583); Common (popmax 24.3%, sas) — too common for a highly-penetrant pathogenic allele; Associated with ATAD5-related disorder.

What condition is associated with ATAD5 p.Pro87Ser (c.259C>T)?

ATAD5 p.Pro87Ser (c.259C>T) is associated with ATAD5-related disorder (ClinVar).

What do computational predictors say about ATAD5 p.Pro87Ser (c.259C>T)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

ATAD5 p.Pro87Ser

Q: How common is ATAD5 p.Pro87Ser (c.259C>T) in the general population?

ATAD5 p.Pro87Ser (c.259C>T) is common (popmax 24.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.259C>T · rs3816780 · VCV3059655

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 24.3%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ATAD5-related disorder

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -5.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.043	GERP -3.3
Regional constraint	o/e 0.98	unconstrained · MANE · 3,612 bp · p 0.54 · regional, not allelic
Overall
CADD	0.73	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.3% South Asian · 21,944/90,378 alleles

Filtering AF 24% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.9%

Overall 12.1% 194,406/1,609,988 alleles · common exomes 174,395/1,459,614 · genomes 20,011/150,374 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	24.3%	4
Admixed American	17.1%	6
African / African-American	16.6%	6
Amishnot grpmax-eligible	16.3%	6
East Asian	15.8%	6
Remaining individualsnot grpmax-eligible	12.4%	8
Middle Eastern	10.9%	9
European (non-Finnish)	10.7%	9
Ashkenazi Jewishnot grpmax-eligible	8.88%	11
Finnishnot grpmax-eligible	8.79%	11

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ATAD5
Protein: p.Pro87Ser
Coding: c.259C>T
MANE Select: NM_024857
dbSNP: rs3816780
Type: single nucleotide variant
Location: chr17:30834340 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.76 · 4 PDB
Residue 87: a UniProt-annotated variant site (in)

Full ATAD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ATAD5-related disorder

Similar variants

ATAD5 c.2956+9T>C Likely benign same condition
ATAD5 c.5456+7G>C Benign same condition
ATAD5 c.5457-7T>G Likely benign same condition
ATAD5 p.Arg1448Cys Benign same condition
ATAD5 p.Arg249Lys Benign same condition
ATAD5 p.Arg52= Likely benign same condition
ATAD5 p.Asn1767Ser Benign same condition
ATAD5 p.Asn699His Benign same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/atad5-p-pro87ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown